1. Field of the Invention
The invention relates to a biochip for the capacitive stimulation and/or detection of biological tissue and to a method for producing such a biochip.
2. Description of the Related Art
Direct communication between nerve cells and electrically active solid-state structures, such as semiconductors for example, has already been a reality on a laboratory scale for a good decade. Successful laboratory trials were reported for example by P. Fromherz et al. in Science 252, 1290 (1991); P. Fromherz et al. in Physical Review Letters 75, 1670 (1995) and also P. Stett et al. in Physical Review E Vol. 55, No. 2, 1779 (1997). A summarizing overview of the early results is contained in P. Fromherz, Berichte der Bunsen Gesellschaft [Reports of the Bunsen Society] No. 7, 1093 (1996). More recently, first biochips produced on industrial scales have also been presented. Modern biochips consequently open up a wide variety of areas of use from basic neurobiological research through to high-throughput-screening applications in the pharmaceutical industry.
A basic element of modern biochips of this type is schematically represented in FIG. 1(a). The biochip comprises a support structure 10, which may comprise, for example, a patterned semiconductor substrate (semiconductor structure). The support structure 10 is separated from an electrolyte 14 by a dielectric layer 12. The corresponding equivalent circuit diagram is represented in FIG. 1(b). In general, the electrically communicating nerve cells are cultivated in an electrolyte directly at those locations on the surface of the support structure 10 at which the active locations of electrical stimulation and detection devices lie.
While in biological systems the electrical activity is carried by ions, in semiconductors electrons or holes are responsible for transporting the charge. Therefore, in a way corresponding to the natural boundary layer between the electrolyte 14 and the semiconductor structure, a capacitive coupling is preferably used both in the stimulation and in the detection of biological processes. This current-free mechanism of electrical coupling between the biochip and the nerve cell to be stimulated or to be detected is based on the principle of electrical induction (electrostatic induction). The electrical coupling is brought about by a charge accumulation in the nerve cell inducing corresponding mirror charges in the biochip, the influence of which, for example on the electrical transporting properties of the support structure 10 formed as a semiconductor structure, can be demonstrated.
Conversely, nerve cells which are arranged on the dielectric layer 12 of the support structure or semiconductor structure 10 can be stimulated by a charge accumulation in a stimulation device of the semiconductor structure 10 inducing charges in the nerve cell. In the case of a biochip of this type, which uses a capacitive coupling to the nerve cell to be investigated both in stimulation processes and in detection processes, the dielectric layer 12 between the semiconductor structure 10 and the electrolyte 14 takes on special significance.
Conventionally, silicone-based, active, and consequently CMOS-capable, semiconductor structures are coated with SiO2, in order to form a dielectric boundary layer or surface layer 12 of this type. However, it has been found that a dielectric layer of SiO2 produces only limitedly satisfactory results, in particular with regard to the coupling efficiency or the achievable signal transfer between the stimulation and/or sensor device of the biochip and the biological tissue to be investigated.
Most recently, TiO2-based dielectric layers have found increasing interest for a large number of technical applications, for example as insulators in MOS structures, as moisture sensors or as passivation layers and protective coatings, on account of such properties as a high dielectric constant, high transparency, photocatalytic behavior and very good chemical resistance. In particular, the high dielectric constant of about 80 along with good passivation properties and good “biocompatibility”, i.e. no substances with adverse effects on cell cultures are detached, make layers of this type of interest for the production of biochips. However, it has been established that TiO2 layers on conductive electrodes, such as for example platinum, exhibit inadequate insulating properties, since the resistance already degrades under very low applied voltages. For example, high conductivities in thin TiO2 (rutile) layers on conductive RuO2 electrodes are also reported in B. H. Park et al., Applied Physics Letters, Vol. 80, No. 7, pages 1174–1176. Moreover, it is known that the conductivity of TiO2 increases greatly even when there are extremely small deviations from the stoichiometric composition; cf. Gmelin Handbuch der anorganischen Chemie [Gmelin handbook of inorganic chemistry], published by Verlag Chemie, 1951, Titan [Titanium], page 251.